A Systematic Analysis of the Clinical Outcome Associated with Multiple Reclassified Desmosomal Gene Variants in Arrhythmogenic Right Ventricular Cardiomyopathy Patients.

ARVC Arrhythmia Composite endpoint Desmosomal genes Genetics Multiple variants

Journal

Journal of cardiovascular translational research
ISSN: 1937-5395
Titre abrégé: J Cardiovasc Transl Res
Pays: United States
ID NLM: 101468585

Informations de publication

Date de publication:
07 Jul 2023
Historique:
received: 21 12 2022
accepted: 07 06 2023
pubmed: 7 7 2023
medline: 7 7 2023
entrez: 7 7 2023
Statut: aheadofprint

Résumé

The presence of multiple pathogenic variants in desmosomal genes (DSC2, DSG2, DSP, JUP, and PKP2) in patients with arrhythmogenic right ventricular cardiomyopathy (ARVC) has been linked to a severe phenotype. However, the pathogenicity of variants is reclassified frequently, which may result in a changed clinical risk prediction. Here, we present the collection, reclassification, and clinical outcome correlation for the largest series of ARVC patients carrying multiple desmosomal pathogenic variants to date (n = 331). After reclassification, only 29% of patients remained carriers of two (likely) pathogenic variants. They reached the composite endpoint (ventricular arrhythmias, heart failure, and death) significantly earlier than patients with one or no remaining reclassified variant (hazard ratios of 1.9 and 1.8, respectively). Periodic reclassification of variants contributes to more accurate risk stratification and subsequent clinical management strategy. Graphical Abstract.

Identifiants

DOI: 10.1007/s12265-023-10403-8 PMID: 37418234
pubmed: 37418234
doi: 10.1007/s12265-023-10403-8
pii: 10.1007/s12265-023-10403-8
doi:

Types de publication

Journal Article

Langues

eng

Sous-ensembles de citation

IM

Subventions

Organisme : NHLBI NIH HHS
ID : R01 HL147064
Pays : United States
Organisme : NHLBI NIH HHS
ID : R01 HL116906
Pays : United States
Organisme : NHLBI NIH HHS
ID : R01 HL164634
Pays : United States
Organisme : NHLBI NIH HHS
ID : R01 HL069071
Pays : United States

Informations de copyright

© 2023. The Author(s).

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Auteurs

Emilia Nagyova (E)

Department of Cardiology, Division Heart & Lungs, University Medical Center Utrecht, University of Utrecht, Heidelberglaan 100, 3584 CX, Utrecht, The Netherlands.
Department of Molecular Biology, Faculty of Natural Sciences, Comenius University in Bratislava, Bratislava, Slovakia.

Edgar T Hoorntje (ET)

Department of Genetics, University Medical Center Groningen, University of Groningen, Groningen, The Netherlands.
Netherlands Heart Institute, Utrecht, The Netherlands.

Wouter P Te Rijdt (WP)

Department of Genetics, University Medical Center Groningen, University of Groningen, Groningen, The Netherlands.
Netherlands Heart Institute, Utrecht, The Netherlands.

Laurens P Bosman (LP)

Department of Cardiology, Division Heart & Lungs, University Medical Center Utrecht, University of Utrecht, Heidelberglaan 100, 3584 CX, Utrecht, The Netherlands.

Petros Syrris (P)

Center for Heart Muscle Disease, Institute of Cardiovascular Science, University College London, London, UK.

Alexandros Protonotarios (A)

Center for Heart Muscle Disease, Institute of Cardiovascular Science, University College London, London, UK.
Nikos Protonotarios Medical Center, 84300, Naxos, Greece.

Perry M Elliott (PM)

Center for Heart Muscle Disease, Institute of Cardiovascular Science, University College London, London, UK.

Adalena Tsatsopoulou (A)

Nikos Protonotarios Medical Center, 84300, Naxos, Greece.

Luisa Mestroni (L)

Cardiovascular Institute, University of Colorado Anschutz Medical Campus, Aurora, CO, USA.

Matthew R G Taylor (MRG)

Cardiovascular Institute, University of Colorado Anschutz Medical Campus, Aurora, CO, USA.

Gianfranco Sinagra (G)

Cardiothoracovascular Department, Azienda Sanitaria-Universitaria Giuliano Isontina (ASUGI), Trieste, Italy.

Marco Merlo (M)

Cardiothoracovascular Department, Azienda Sanitaria-Universitaria Giuliano Isontina (ASUGI), Trieste, Italy.

Yuko Wada (Y)

Department of Medicine, Vanderbilt University Medical Center, Nashville, TN, USA.
Department of Cardiovascular Medicine, Shiga University of Medical Science, Otsu, Japan.

Minoru Horie (M)

Department of Cardiovascular Medicine, Shiga University of Medical Science, Otsu, Japan.

Jens Mogensen (J)

Department of Cardiology, Aalborg University Hospital, Aalborg, Denmark.

Alex H Christensen (AH)

Department of Cardiology, Herlev-Gentofte and Rigshospitalet, Copenhagen University Hospital, Copenhagen, Denmark.

Brenda Gerull (B)

Department of Cardiac Sciences, Libin Cardiovascular Institute of Alberta, Calgary, AB, Canada.
Comprehensive Heart Failure Center (CHFC) and Department of Internal Medicine I, University Hospital Würzburg, Würzburg, Germany.

Lei Song (L)

Arrhythmia Center and Clinical EP Laboratory, State Key Laboratory of Cardiovascular Diseases, National Center for Cardiovascular Disease, Fuwai Hospital, Peking Union Medical College-Chinese Academy of Medical Sciences, Beijing, China.

Yan Yao (Y)

Arrhythmia Center and Clinical EP Laboratory, State Key Laboratory of Cardiovascular Diseases, National Center for Cardiovascular Disease, Fuwai Hospital, Peking Union Medical College-Chinese Academy of Medical Sciences, Beijing, China.

Siyang Fan (S)

Arrhythmia Center and Clinical EP Laboratory, State Key Laboratory of Cardiovascular Diseases, National Center for Cardiovascular Disease, Fuwai Hospital, Peking Union Medical College-Chinese Academy of Medical Sciences, Beijing, China.

Ardan M Saguner (AM)

Department of Cardiology, University Heart Center, Zurich, Switzerland.

Firat Duru (F)

Department of Cardiology, University Heart Center, Zurich, Switzerland.

Juha W Koskenvuo (JW)

Blueprint Genetics, Helsinki, Finland.

Tania Cruz Marino (T)

Department of Medical Biology, CIUSSS Saguenay Lac-St-Jean, Chicoutimi, QC, Canada.

Crystal Tichnell (C)

Division of Cardiology, Department of Medicine, Johns Hopkins University School of Medicine, Baltimore, USA.

Daniel P Judge (DP)

Division of Cardiology, Department of Medicine, Medical University of South Carolina, Charleston, USA.

Dennis Dooijes (D)

Department of Genetics, University Medical Center Utrecht, University of Utrecht, Utrecht, the Netherlands.
.

Ronald H Lekanne Deprez (RH)

.
Department of Human Genetics, Amsterdam University Medical Center, University of Amsterdam, Amsterdam, the Netherlands.

Cristina Basso (C)

.
Department of Cardiac-Thoracic-Vascular Sciences and Public Health, University of Padua, Padua, Italy.

Kalliopi Pilichou (K)

.
Department of Cardiac-Thoracic-Vascular Sciences and Public Health, University of Padua, Padua, Italy.

Barbara Bauce (B)

Department of Cardiac-Thoracic-Vascular Sciences and Public Health, University of Padua, Padua, Italy.

Arthur A M Wilde (AAM)

.
Heart Center, Department of Clinical and Experimental Cardiology, Amsterdam University Medical Center, University of Amsterdam, Amsterdam, the Netherlands.

Philippe Charron (P)

APHP, Referral Center for Cardiac Hereditary Diseases, Sorbonne University, Pitié-Salpêtrière Hospital, Paris, France.

Véronique Fressart (V)

APHP, Referral Center for Cardiac Hereditary Diseases, Sorbonne University, Pitié-Salpêtrière Hospital, Paris, France.

Jeroen F van der Heijden (JF)

Department of Cardiology, Division Heart & Lungs, University Medical Center Utrecht, University of Utrecht, Heidelberglaan 100, 3584 CX, Utrecht, The Netherlands.

Maarten P van den Berg (MP)

Department of Cardiology, University of Groningen, University Medical Center Groningen, Groningen, the Netherlands.

Folkert W Asselbergs (FW)

Department of Cardiology, Division Heart & Lungs, University Medical Center Utrecht, University of Utrecht, Heidelberglaan 100, 3584 CX, Utrecht, The Netherlands.
.
Institute of Cardiovascular Science, Faculty of Population Health Science, University College London, London, UK.
Health Data Research UK and Institute of Health Informatics, University College London, London, UK.

Cynthia A James (CA)

Division of Cardiology, Department of Medicine, Johns Hopkins University School of Medicine, Baltimore, USA.

Jan D H Jongbloed (JDH)

Department of Genetics, University Medical Center Groningen, University of Groningen, Groningen, The Netherlands.

Magdalena Harakalova (M)

Department of Cardiology, Division Heart & Lungs, University Medical Center Utrecht, University of Utrecht, Heidelberglaan 100, 3584 CX, Utrecht, The Netherlands. m.harakalova@umcutrecht.nl.
Netherlands Heart Institute, Utrecht, The Netherlands. m.harakalova@umcutrecht.nl.
Regenerative Medicine Utrecht (RMU), University Medical Center Utrecht, University of Utrecht, Utrecht, The Netherlands. m.harakalova@umcutrecht.nl.
ORCID: 0000-0002-7293-1029

J Peter van Tintelen (JP)

Netherlands Heart Institute, Utrecht, The Netherlands.
.
Department of Human Genetics, Amsterdam University Medical Center, University of Amsterdam, Amsterdam, the Netherlands.
Department of Genetics, University Medical Center Utrecht, University of Utrecht, Utrecht, the Netherlands.

Classifications MeSH